The transformation of normal human mammary epithelium to carcinoma is currently understood primarily in morphological, growth and cell behavioral terms. Limited information is available on the biochemistry in this differentiation process. Specific gene activation and repression, reflected in expression of enzymes, their isozymes and structural proteins are the fundamental mechanisms by which the development and progression of a carcinoma are controlled. In this study, I intend to establish systematically the enzyme and isozyme differences between normal and malignant human mammary epithelium; the effect of mammotropic hormones on differential isozyme expression; and whether this is useful in diagnosis and prognosis of breast cancer. The studies are being carried out using a defined system to culture normal and malignant mammary epithelium. Work in progress indicates that normal and malignant human mammary epithelium exhibit apparent differences in some specific enzyme and isozyme expression and such differences are applicable to normal and neoplastic breast tissues derived from in vivo. Efforts are being made to identify and characterize additional isozymes unique in type or amount in neoplastic human breast cells. The possibility of using these isozymes as diagnostic and prognostic markers for breast cancer will be assessed.